Adenosine A2A receptor activation on CD4+ T lymphocytes and neutrophils attenuates lung ischemia–reperfusion injury
| Autor: | Victor E. Laubach, Susan I. Ramos, Joel Linden, Zequan Yang, Yunge Zhao, George J. Stukenborg, Ashish Sharma, Irving L. Kron |
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| Rok vydání: | 2010 |
| Předmět: |
CD4-Positive T-Lymphocytes
Lung Diseases Male Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty Adenosine A2 Receptor Agonists T cell Adenosine A2A receptor Vascular permeability Lung injury Pharmacology Article Capillary Permeability 03 medical and health sciences Mice 0302 clinical medicine Piperidines medicine Animals 030304 developmental biology 0303 health sciences medicine.diagnostic_test business.industry medicine.disease Adenosine receptor Immunohistochemistry 3. Good health Respiratory Function Tests Mice Inbred C57BL medicine.anatomical_structure Bronchoalveolar lavage Neutrophil Infiltration 030220 oncology & carcinogenesis Reperfusion Injury Cytokines Surgery Interleukin 17 Chemokines business Cardiology and Cardiovascular Medicine Reperfusion injury |
| Zdroj: | The Journal of Thoracic and Cardiovascular Surgery. 139(2):474-482 |
| ISSN: | 0022-5223 |
| DOI: | 10.1016/j.jtcvs.2009.08.033 |
| Popis: | Objective Adenosine A 2A receptor activation potently attenuates lung ischemia–reperfusion injury. This study tests the hypothesis that adenosine A 2A receptor activation attenuates ischemia–reperfusion injury by inhibiting CD4+ T cell activation and subsequent neutrophil infiltration. Methods An in vivo model of lung ischemia–reperfusion injury was used. C57BL/6 mice were assigned to either sham group (left thoracotomy) or 7 study groups that underwent ischemia–reperfusion (1 hour of left hilar occlusion plus 2 hours of reperfusion). ATL313, a selective adenosine A 2A receptor agonist, was administered 5 minutes before reperfusion with or without antibody depletion of neutrophils or CD4+ T cells. After reperfusion, the following was measured: pulmonary function using an isolated, buffer-perfused lung system, T cell infiltration by immunohistochemistry, myeloperoxidase and proinflammatory cytokine/chemokine levels in bronchoalveolar lavage fluid, lung wet/dry weight, and microvascular permeability. Results ATL313 significantly improved pulmonary function and reduced edema and microvascular permeability after ischemia–reperfusion compared with control. Immunohistochemistry and myeloperoxidase content demonstrated significantly reduced infiltration of neutrophils and CD4+ T cells after ischemia–reperfusion in ATL313-treated mice. Although CD4+ T cell–depleted and neutrophil-depleted mice displayed significantly reduced lung injury, no additional protection occurred when ATL313 was administered to these mice. Expression of tumor necrosis factor-α, interleukin 17, KC, monocyte chemotactic protein-1, macrophage inflammatory protein-1, and RANTES were significantly reduced in neutrophil- and CD4+ T cell–depleted mice and reduced further by ATL313 only in neutrophil-depleted mice. Conclusions These results demonstrate that CD4+ T cells play a key role in mediating lung inflammation after ischemia–reperfusion. ATL313 likely exerts its protective effect largely through activation of adenosine A 2A receptors on CD4+ T cells and neutrophils. |
| Databáze: | OpenAIRE |
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